Lung cancer is the leading cause of cancer mortality worldwide. A possible carcinogenic role of human papillomavirus (HPV) has been investigated for >20 years and has major clinical and public health implications. We performed a meta-analysis to assess the prevalence of HPV16 and HPV18 in primary lung cancers (2435 subjects from 37 published studies). The overall HPV prevalence ranged from 0.0 to 78.3% with large heterogeneity across geographic regions and histological tissue types. A higher proportion, 50% (7/14), of the European studies reported low or no HPV prevalence (0-10%) compared with the Asian studies, 22% (4/18). When the analysis was limited to HPV16 and HPV18 prevalence, a higher prevalence in Asia (HPV16 = 11.6% and HPV18 = 8.8%) than in Europe (HPV16 = 3.5% and HPV18 = 3.6%) was observed. Studies using HPV-specific primers resulted in higher prevalence rates than consensus HPV primers (HPV16: Asia = 13% and Europe = 6%; HPV18: Asia = 13% and Europe = 5%). Further studies are needed to elucidate the role of HPV in lung carcinogenesis with careful thought given to study design and laboratory detection methods for a more accurate assessment of HPV status in lung tumors.